Transplantation of human umbilical cord blood-derived cellular fraction improves left ventricular function and remodeling after myocardial ischemia/reperfusion

Abstract

RATIONALE: Human umbilical cord blood (hUCB) contains diverse populations of stem/progenitor cells. Whether hUCBderived nonhematopoietic cells would induce cardiac repair remains unknown. OBJECTIVE: To examine whether intramyocardial transplantation of hUCB-derived CD45-Lin-nonhematopoietic cellular fraction after a reperfused myocardial infarction in nonimmunosuppressed rats would improve cardiac function and ameliorate ventricular remodeling. METHODS AND RESULTS: Nonhematopoietic CD45-Lin-cells were isolated from hUCB. Flow cytometry and quantitative polymerase chain reaction were used to characterize this subpopulation. Age-matched male Fischer 344 rats underwent a 30-minute coronary occlusion followed by reperfusion and 48 hours later received intramyocardial injection of vehicle or hUCB CD45-Lin-cells. After 35 days, compared with vehicle-treated rats, CD45-Lin-cell-treated rats exhibited improved left ventricular function, blunted left ventricular hypertrophy, greater preservation of viable myocardium in the infarct zone, and superior left ventricular remodeling. Mechanistically, hUCB CD45-Lin-cell injection favorably modulated molecular pathways regulating myocardial fibrosis, cardiomyocyte apoptosis, angiogenesis, and inflammation in postinfarct ventricular myocardium. Rare persistent transplanted human cells could be detected at both 4 and 35 days after myocardial infarction. CONCLUSIONS: Transplantation of hUCB-derived CD45-Lin-nonhematopoietic cellular subfraction after a reperfused myocardial infarction in nonimmunosuppressed rats ameliorates left ventricular dysfunction and improves remodeling via favorable paracrine modulation of molecular pathways. These findings with human cells in a clinically relevant model of myocardial ischemia/reperfusion in immunocompetent animals may have significant translational implications. VISUAL OVERVIEW: An online visual overview is available for this article.